DE
Neuronal response to emerging viral infections
Summary
Nearly half of all emerging viral infections (EVIs) cause neurological symptoms, and around 40% are linked to serious brain infections like encephalitis. Viruses such as enterovirus A71, D68, measles, or flaviviruses can trigger brain inflammation, sometimes after mild illnesses. In some cases, the immune system’s strong response can itself lead to brain damage.
This project investigates how the brain’s own immune defenses respond to such viruses—and how this response can be both protective and harmful. The focus is on specific immune genes, like those in the apolipoprotein L family, which help fight infections but may also damage nerve cells. Understanding this balance could lead to new strategies to prevent or treat long-term neurological effects caused by EVIs.
Our Work Packages (WP):
WP1: Characterization of the antiviral and neurotoxic molecular mechanism of APOL6.
WP2: Identification of pathways involved in the antiviral function of APOL6 in vivo.
WP3: Translatability and profiling of neuronal proteins with virus-selective antiviral properties.
These work packages help us to unravel how antiviral defenses in neurons contribute to both protection and damage - and to assess the neurological risk posed by emerging viruses.
Team
Prof. Dr. Manuel Friese
Principal Investigator
E-mail address:
Phone: +49 (0) 40 7410 - 57277
Research Group Friese
The Research Group Neuroimmunology and Multiple Sclerosis is based at the University Medical Center Hamburg-Eppendorf (UKE).
Project related publications
Woo MS, Shafiq M, Fitzek A, …, Addo MM, Schulze Zur Wiesch J, Ondruschka B, Friese MA#, Glatzel M#. Vagus nerve inflammation contributes to dysautonomia in COVID-19. Acta Neuropathol. 2023 Sep;146(3):387–394. doi: 10.1007/s00401-023-02612-x.
Rothammer N, Woo MS, Bauer S, Binkle-Ladisch L, …, Merkler D, Engler JB#, Friese MA#. G9a dictates neuronal vulnerability to inflammatory stress via transcriptional control of ferroptosis. Sci Adv. 2022;8:eabm5500. doi: 10.1126/sciadv.abm5500.
Krasemann S, Haferkamp U, Pfefferle S, …, Friese MA, Glatzel M#, Pless O#. The blood-brain barrier is dysregulated in COVID-19 and serves as a CNS entry route for SARS-CoV-2. Stem Cell Reports. 2022;17:307–320. doi: 10.1016/j.stemcr.2021.12.011.
Woo MS, Ufer F, Rothammer N, …, Pless O, Merkler D, Friese MA. Neuronal metabotropic glutamate receptor 8 protects against neurodegeneration in CNS inflammation. J Exp Med. 2021;218:e20201290. doi: 10.1084/jem.20201290.
Woo MS, Haag F, Nierhaus A, …, Addo MM, Schmiedel S, Friese MA#, Kluge S#, Schulze Zur Wiesch J#. Multi-dimensional and longitudinal systems profiling reveals predictive pattern of severe COVID-19. iScience. 2021;24:102752. doi: 10.1016/j.isci.2021.102752.
Woo MS, Malsy J, Pöttgen J, …, Addo MM, …, Heesen C, Schulze Zur Wiesch J#, Friese MA#. Frequent neurocognitive deficits after recovery from mild COVID-19. Brain Commun. 2020 Nov 23;2(2):fcaa205. doi: 10.1093/braincomms/fcaa205.
Schattling B, Engler JB, Volkmann C, …, Gundelfinger ED, Merkler D, Friese MA. Bassoon proteinopathy drives neurodegeneration in multiple sclerosis. Nat Neurosci. 2019;22:887–896. doi: 10.1038/s41593-019-0385-4.
Stanelle-Bertram S, Walendy-Gnirß K, Speiseder T, …, Friese MA, …, Löscher W, Calderon de Anda F, Gabriel G. Male offspring born to mildly ZIKV-infected mice are at risk of developing neurocognitive disorders in adulthood. Nat Microbiol. 2018 Oct;3(10):1161–1174. doi: 10.1038/s41564-018-0236-1.
Dendrou CA, Fugger L, Friese MA. Immunopathology of multiple sclerosis. Nat Rev Immunol. 2015 Sep 15;15(9):545–558. doi: 10.1038/nri3871.
#equally contributing authors